We have established that HLA antigens are present in human serum in addition to being present on cell membranes. The serum levels of each of 28 antigens of the first and second segregant series vary considerably. The levels of HLA-A9 in normals were eight to 16-fold higher than the levels of most other HLA specificities. Hyper- cholesterodemia patients appear to have serum HLA levels which are within the normal range. Serum HLA-A9 was found to be present in the serum high density lipoprotein (HDL) fraction. By isolating this fraction the serum HLA antigen could be purified free from the major serum protein. The HDL has one major and five minor protein components. A minor protein component of MW 84,000 was present only in HDL with high HLA activity and seems to be likely candidate for the HLA antigen. The native antigen in serum has a molecular weight (MW) of 200-300,000 which corresponds to the MW of HDL. Antisera were raised to papain sobulised antigens from maligant spleens from lymphoma patients and they were tested by complement-dependent cytotoxicity and immunoflurescent staining against various normal and leukemic target cells. The antigen detected by this antisera is present on leukemic cells from 75% of all subclasses of leukemic patients and also normal peripheral B lymphocytes. Normal T lymphocytes, granulocytes, platelets and erythrocytes do not express the antigen. In several patients the numbers of fluorescein positive cells were counted before and after chemotherapy and agreed well with the fall in the numbers of leukemia blast cells determined by morphological examination. Bibliographic references: Bonner, J., Garrard, W., Gottesfeld, J., Billing, R.J., and Uphouse, L.: Isolation of template active and inactive regions of chromatin. Methods in Enzymology XL part E: 97, 1975. Ferrone, S., Pellegrino, M.A., Billing, R.J., Terasaki, P.I., and Reisfeld, R.A.: The production of anti W24 xenoantisera in rabbits. Tissue Antigens 5: 41, 1975.